The HOMA IR strongly correlated with the clamp IR in type 2 diabetic patients treated with SUs as well as in those treated with diet alone.

Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.

Objective: Subclinical hypothyroidism affects 5-15% of the general population and is associated with increased morbidity from cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a parameter of arterial stiffening and a good independent predictor for the presence of coronary artery disease. This study was performed to assess whether subclinical hypothyroidism might cause enhanced baPWV.Patients and Methods: baPWV was examined in subclinical hypothyroid patients (n ϭ 50) and normal control subjects (n ϭ 50).Results: Diastolic blood pressure (DBP), a main risk factor for cardiovascular disease, and baPWV were both significantly higher in subclinical hypothyroid patients than normal subjects. baPWV was significantly positively correlated with age and systolic, diastolic, and pulse pressure and significantly negatively correlated with pulse rate in both subclinical hypothyroid patients and normal subjects. In contrast, there was no significant correlation of baPWV with free T 3 , free T 4 , TSH, total, high-density lipoprotein-and low-density lipoproteincholesterol, and the preejection time to ejection time ratio. A comparison of individual values of baPWV and DBP and regression slopes in two groups revealed that baPWV values increase to a larger extent than the increase in DBP in subclinical hypothyroid patients. In both groups, stepwise regression analysis showed a significant and independent association of DBP with baPWV. Conclusions:The present study demonstrated significant increases of baPWV and DBP in subclinical hypothyroid patients. Furthermore, the results suggest that increased DBP might be one of the main factors responsible for increased arterial stiffening in subclinical hypothyroid patients.

Objective: Subclinical hypothyroidism affects 5-15% of the general population, is especially prevalent in females, and may be associated with increased morbidity from cardiovascular disease, although it remains controversial. We recently reported a significant increase in the brachial-ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor of cardiovascular events, in subclinical hypothyroidism without thyroiditis. The current study was performed to assess changes in baPWV in female subclinical hypothyroidism with autoimmune chronic thyroiditis (Hashimoto's disease) after restoration of normal thyroid function. Methods: In a randomized placebo-controlled study, 95 female subclinical hypothyroid patients were monitored for changes in baPWV before and after levothyroxine (L-T 4 ) replacement therapy. Changes in baPWV were also measured in 42 age-matched normal female subjects. Results: The baseline baPWV values in patients with subclinical hypothyroidism were significantly higher than in normal subjects. With attainment of euthyroidism, baPWV showed a significant decrease from 1776.7G86.0 to 1674.3G79.2 cm/s (PZ0.006) in patients treated with L-T 4 , but the changes in baPWV and TSH were not correlated. The change in baPWV was significantly and negatively correlated with age and baseline pulse pressure, but multiple regression analysis revealed that these parameters failed to be associated with the change in baPWV. Conclusions: Sustained normalization of thyroid function during L-T 4 replacement therapy significantly decreases baPWV in female subclinical hypothyroid patients with autoimmune chronic thyroiditis, suggesting the improvement of arterial stiffening and, consequently, possible prevention of cardiovascular disease.

Sitagliptin reduces the ACR through decreasing both blood pressure and eGFR, with no correlation with a decrease in HbA1c over a 3-month period. These results may reflect the direct action of sitagliptin on the kidneys.

Calcification is almost invariably associated with atherosclerotic plaque lesions. Recent data suggest that plaque calcification is an active, regulated process similar to osteogenesis. In order to clarify the mechanism of plaque calcification, we developed an in vitro model of vascular calcification by utilizing bovine vascular smooth muscle cells (BVSMCs). This model is useful in that diffuse and massive calcification can be induced within 2 weeks and thereby biochemical analyses of vascular calcification can be performed. We have analyzed several aspects of vascular calcification by using this model and demonstrated as follows: 1) in vitro calcification of BVSMCs is regulated by calciotropic hormones and BVSMCs are equipped with a unique autocrine and/or paracrine system regulating calcium metabolism. 2) Sodium-dependent phosphate cotransport plays a crucial role in BVSMC calcification as well as in mineralization of skeletal tissues. 3) BVSMCs acquire osteoblastic phenotype under certain conditions. Finally, we discuss the roles of macrophages in the development of atherosclerotic calcification. Interferon-gamma (IFN-gamma) induces gene expression of 25-hydrovitamin D-1 alpha-hydroxylase (1 alpha OHase) and its activity in macrophages. Since 1 alpha OHase can locally convert 25-hydroxyvitamin D into 1 alpha, 25-dihydroxyvitamin D (1,25(OH)2D), an active metabolite of vitamin D, it is suggested that local production of 1,25(OH)2D by macrophages may promote atherosclerotic calcification. Moreover, macrophages may be involved in the phenotypic changes of vascular smooth muscle cells (VSMCs) to acquire calcifying capacity. Therefore, the phenotypic changes of VSMCs in atherosclerotic plaque may contribute to the development of atherosclerotic calcification.

Leptin is a newly found hormone secreted by adipocytes [1]. It is the ob gene product which regulates food intake and thermogenesis [2][3][4]. The ob/ob mouse has a mutation in the ob gene [1], and db/db mice have a mutation in the gene coding for the leptin receptor [5,6]. Therefore, leptin could play an important role in the pathogenesis of obesity and diabetes mellitus. In humans, however, the majority of obese subjects have elevated plasma leptin concentrations [7][8][9], suggesting the presence of leptin resistance [10]. The mechanisms regulating plasma leptin level or leptin resistance are not fully understood. Body fatness was one of the important determinants of plasma leptin levels [7][8][9]. Some studies showed that insulin infusion increased plasma leptin concentration [11,12], although other studies [13] did not. One report [13] indicated that insulin resistance was associated with elevated plasma leptin concentrations independent of body fat, whereas more recent studies [14,15] failed to detect the independent contribution of insulin sensitivity or body fat distribution, an indicator of insulin resistance [16], to plasma leptin concentration. In addition, there is a possibility that renal function may play an important role in the regulation of plasma leptin concentration. Renal impairment results in insulin resistance and hyperinsulinaemia [17]. Also, the kidney is among the organs expressing leptin receptors [18], although their functions are unknown at present. To answer these controversies and to evaluate the possible impact of renal function on leptin, we performed the euglycaemic hyperinsulinaemic clamp in 57 patients with non-insulin-dependent diabetes mellitus (NIDDM). The results suggest that: 1) both total mass and distribution of body fat are important determinants of leptin levels; 2) leptin Diabetologia (1997) 40: 676-679 Renal function and insulin resistance as determinants of plasma leptin levels in patients with NIDDM Summary Plasma leptin level is known to correlate with the degree of obesity. To determine the influences of renal fuction and insulin resistance on plasma leptin concentrations, we measured plasma leptin concentrations and performed the euglycaemic hyperinsulinaemic clamp studies in 57 patients with non-insulin-dependent diabetes mellitus with a wide range of renal function. In simple regression analyses, plasma leptin concentration showed significant positive correlations with percentage of body fat measured by dual energy X-ray absorptiometry, body mass index, waist to hip ratio and fasting plasma insulin. Leptin level was higher in females than males.Multiple regression analyses indicated that percent body fat, waist to hip ratio, plasma insulin, gender and renal function (1/creatinine), but not insulin sensitivity, were significant and independent determinants of plasma leptin level. These results suggest that plasma leptin level is regulated or affected by multiple factors including renal function. Insulin resistance appeared to increase leptin levels indirectl...

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